To investigate the usefulness of nicorandil as an antianginal drug, we compared the coronary vasodilatory response in nonstenotic coronary artery segments and the hemodynamic response in 26 coronary artery disease patients. Both responses were studied prior to sublingual administration of 10mg of this drug and 10, 30 and 60min afterward. The plasma nicorandil concentration was determined up to 120min after administration. The mean coronary dilating ratio of nicorandil was 117% 30min after administration (p<0.01) and showed a good correlation to the plasma nicorandil concentration. The mean maximum dilating ratio of each patient was 125%. There was no difference between individual coronary arteries or between proximal and distal segments in terms of the coronary artery dilating ratio. The plasma nicorandil concentration required for 120% dilation of the coronary arteries was 26ng/ml, 89ng/ml and 142ng/ml for those cases with variant angina, exertional angina and postinfarction angina, respectively. Hemodynamic changes due to administration of this drug included a decrease in blood pressure, and a reduction in total peripheral resistance, rate-pressure product, pulmonary capillary pressure and stroke-work index. These results indicate that the antianginal effects of nicorandil are derived from its coronary vasodilatory action and an inhibitory effect on myocardial oxygen consumption.

View full abstract

In order to assess diastolic overload by electrocardiogram (ECG), we performed body surface ECG mapping (MAP), and then compared the results with echocardiographic, roentgenographic and cardiac catheterization findings. Eighty-seven unipolar electrocardiograms were simultaneously recorded for the following groups: 1) 40 normal subjects, 2) 46 patients with diastolic overload [32 patients with aorticregurgitation (AR) and 14 patients with mitral regurgitation (MR)]. QRS isopotential maps were constructed at 10, 20, 30, 40, 50 and 60 msec from the QRS onset. On the potential departure map, the area where the QRS voltage was greater than the normal limits (mean+2SD of normal control) was designated as "+2SD area". In patients with diastolic overload, +2SD area was found on the left anterior chest and back at 40, 50 and 60 msec from QRS onset. Subjects were classified into the following 3 groups according to the location of their +2SD area: 1) group A (n=23) in which the +2SD area was found on the left anterior chest and back, 2) group B (n=17) in which the +2SD area was found only on the back, and 3) group N (n=6) in which no +2SD area was found. Group A had a markedly greater left ventricular end-diastolic internal dimension than the other groups (A 63.6±6.8mm, B 53.9±5.5mm, N 50.7±6.0mm, A vs. B, N p<0.01), and a greater cardiothoracic ratio than the other groups (A 58.5±5.6%, B 52.5±7.0%, N 52.3±4.7%, A vs. B, N p<0.01). There was no significant difference in wall thickness among the 3 groups. The regurgitation severity assessed by cardiac catheterization was greater in group A than in the other groups. Among AR patients, the +2SD area was located on the upper back and the upper anterior chest, whereas among MR patients, it tended to be located on the lower portions. The potential departure map is a useful noninvasive analytic method for determining the extent and grade of diastolic overload. Furthermore, the location of the +2SD area may be used to discriminate between AR and MR.

View full abstract

Catheter balloon mitral valvuloplasty (BMV) was performed in 50 patients and 32 of them undergoing BMV with double balloon technique were studied to evaluate the usefulness of echocardiography in the prediction of early results of BMV. Five echocardiographic variables including mitral valve motion, mitral valve thickness, subvalvular change, commissural calcification and left atrial dimension were evaluated. Each variable was divided into mild, moderate and severe subgroups. Before valvuloplasty there were no differences in mitral valve area among any subgroup for any variable. After valvuloplasty, variables associated with a greater increase in mitral valve area from mild and moderate subgroups than from severe subgroup included mitral valve motion, mitral valve thickness, and subvalvular change, but not commissural calcification or left atrial dimension, We scored the former 3 variables as 0, 1 and 2 points in the mild, moderate and severe subgroups, respectively. The sums of individual scores in these 3 variables were further divided into 3 groups: 12 patients had a lower score (<2), 10 patients had a score of 3-4 and 10 patients had a higher score (>5). Patients with lower scores tended to have greater increases in mitral valve areas after valvuloplasty than those with higher scores.
Thus, mitral valve motion, mitral valve thickness and subvalvular change may be useful to predict a greater increase in mitral valve area after valvuloplasty. A lower score of echocardiographic variables anticipates successful balloon mitral valvuloplasty, which may be helpful in patient selection.

View full abstract

Right-sided endocarditis is rare in children. Since the clinical picture is nonspecific and the frequency of sterile blood cultures is high, the clinical and laboratory diagnosis is difficult. Recent reports suggest that echocardiography is a useful method to detect the presence of right-sided endocarditis.
We studied 8 patients with congenital heart disease and right-sided endocarditis detected by two-dimensional echocardiography. All the patients were shown to have one or more vegetations in the two-dimensional echocardiographic examination. The 4 patients who did not respond to antibiotic therapy underwent elective cardiac surgery. One of these patients additionally had recurrent emboli to the lungs. Another of these 4 patients died during surgery due to myocardial failure. Apart from these 4 cases, urgent surgical intervention had to be carried out in 2 cases because of very large vegetative masses. Surgical confirmation of the diagnosis was available in all 6 cases.
According to these results, we can conclude that two-dimensional echocardiography assumes a specific diagnostic role in cases with rightsided endocarditis.

View full abstract

Sixty two black patients who had confirmed but untreated hypertension participated in a double blind clinical trial of the efficacy and tolerability of slow-release oxprenolol in a daily dose of 160mg initially and 320mg subsequently versus chlorthalidone 50mg daily. Thereafter, a combination of oxprenolol with chlorthalidone in an initial dose of 160mg and 25mg and a subsequent dose of 320mg and 50mg, respectively, was administered and the effects compared with those of the same drugs given singly. The trial lasted for 3 years, but each participant took active medication for 1 year.
Oxprenolol as monotherapy had no effect on the blood pressure, irrespective of the dose. Chlorthalidone as monotherapy produced a significant fall in blood pressure (p<0.01). Combining the 2 drugs enhanced their blood pressure lowering effects (p<0.001). Oxprenolol as monotherapy and as part of combination therapy was well tolerated by all patients. Chlorthalidone as monotherapy was well tolerated by most patients while a fraction of the patients developed biochemical derangements.
These results confirm the findings that a beta-blocker alone may be ineffective in lowering blood pressure in hypertensive blacks. The results also show that the efficacy and tolerability of a beta-blocker and a diuretic are enhanced by their combined administration. Finally, the results show that increasing the dose of a beta-blocker or a diuretic does not pro-duce a further increase in its blood pressure lowering effect.

View full abstract

Abana is a herbomineral medicinal preparation with a property of down-regulation of beta-adrenergic receptors. A double-blind, parallel group study was conducted in 43 Indian men and women suffering from hypertension to evaluate the antihypertensive effect of Abana and compare it with that of methyldopa (M-DOPA). Twenty-one patients received 800mg tds of Abana and 22 patients received 250mg tds of MDOPA for 4 weeks. Blood pressure and pulse rate were recorded at weekly intervals. Relevant clinical and biochemical investigations were carried out before and after treatment.
In patients treated with Abana, there was a significant fall both in systolic B.P. (from 167±3.73 to 145±6.11mmHg) and in diastolic B.P. (from 110±1.86 to 91±3.04mmHg) at the end of 4 weeks. Similarly in patients treated with M-DOPA, systolic blood pressure was significantly reduced from 165±4.92 to 146±4.9mmHg and diastolic blood pressure was reduced from 106±2.74 to 96±2.67mmHg after 4 weeks. The onset of antihypertensive effect was earlier and there was a higher percentage of responders (80%) in the Abana-treated group. None of the patients had clinically or biochemically significant side-effects. The results of this study suggest that therapy with Abana proved highly effective in hypertensive patients.

View full abstract

This study examined the effects of human umbilical vein endothelial cells (ECs) and calcium channel blockers (Ca²⁺ blockers), diltiazem, verapamil, and nicardipine, on platelet aggregation in vitro. ECs markedly inhibited the platelet aggregation induced by ADP, collagen, thromboxane A₂ (TXA₂), or thrombin. When platelets were incubated with ECs, the antiaggregatory activity reached a plateau within 5 to 10min. As the number of ECs added to the platelet-rich plasma was increased, platelet aggregation declined progressively. The antiaggregatory activity of ECs was attenuated considerably by the addition of aspirin. All three Ca²⁺ blockers inhibited platelet aggregation in a dose-dependent manner. The combination of ECs and a Ca2+ blocker resulted in more potent inhibition of platelet aggregation than either alone, but the effects were not synergistic. Both ECs and Ca²⁺ blockers inhibited the synthesis of TXA2 during platelet aggregation. However, Ca²⁺ blockers did not significantly influence the production of prostaglandin I₂ (PGI₂) by ECs during incubation and aggregation. These results suggest that PGI₂ is an important factor in endothelial antiaggregatory activity. Ca²⁺ blockers directly inhibit platelet aggregation by suppressing TXA₂ formation, but do not appear to enhance the antiaggregatory activity of ECs.

View full abstract

The cardiovascular effects of the novel compound WEB 1881-FU (4-amino-methyl-1-benzyl-pyrrolidine-2-one-fumarate) were investigated using cross-circulated dog atrial preparations. Intravenous injections of WEB 1881 induced a hypotensive effect with slight tachycardia at a large dose in anesthetized dogs. At the same time, it produced slight positive chronotropic and inotropic effects in the isolated atrium perfused with the donor's arterial blood. Direct injections of WEB 1881 into the sinus node artery of the isolated and perfused atrium induced positive chrono and inotropic effects in a relatively small dose range. At higher doses, it caused biphasic chrono- and inotropic effects, i.e., initial brief negative effects followed by long-lasting positive chrono- and inotropic effects. The negative chrono- and inotropic responses to WEB 1881 were not blocked by atropine in doses which significantly suppressed ACh-induced negative chrono- and inotropic responses. The positive chrono- and inotropic responses to WEB 1881 were significantly inhibited either by a beta-blocker (propranolol) or by an uptake blocker (imipramine). From these results, it is concluded that WEB 1881 has a tyramine-like, catecholamine releasing property. Although a large dose of WEB 1881 has a direct cardiac depressant action, it does not affect muscarinic mechanisms in the heart.

View full abstract

In order to investigate the effects of atrial natriuretic polypeptides (ANP) on hypertensive glomerular lesions, ANP was administered intravenously by osmotic minipumps to 20 15-week-old male spontaneously hypertensive rats (SHRs) in a sustained hypertensive stage. ANP was infused at the rate of 100ng/hour/rat (the ANP group). Saline was similarly administered to 19 age-matched SHRs (the control group). The rats were sacrificed on the seventh day. Semiquantitative evaluation of the renal tissue revealed no significant difference in glomerular sclerosis between the 2 groups. However, segmental hyalinosis in glomeruli was more accentuated in the ANP group than in the control group. As it is suggested that hyalinosis in glomeruli is related to the elevated intracapillary pressure, the results of the present work were in accordance with reports that ANP increases glomerular capillary pressure by preglomerular vasodilation and postglomerular vasoconstriction. It should be determined whether endogenous ANP works as an aggravating factor for glomerular injuries in the natural course of hypertension.

View full abstract

To determine the significance of vasopressin in cardiovascular and neurohormonal responses caused by centrally administered hypertonic NaCl, we examined the effects of a vasopressin antagonist on blood pressure, heart rate, plasma levels of catecholamines, cortisol and renin activity in anesthetized dogs.
Intracerebroventricular (ICV) injections of 0.2ml of 1.5M NaCl increased mean arterial blood pressure (+29.7±3.0mmHg, mean±SE), heart rate (+27.9±7.0 beats/min), plasma concentrations of vasopressin (+48.9±8.2pg/ml), norepinephrine (+40.0±6.2pg/ml), epinephrine (+231.4±21.4pg/ml) and cortisol (+5.3±1.1μg/dl) and decreased plasma renin activity (-2.0±0.4ng/ml/hr). An intravenous vasopressin antagonist, d(CH₂)₅Tyr(Me)AVP, at a dose of 10μg/kg, attenuated the pressor response and augmented the heart rate response to ICV 1.5M NaCl. The vasopressin antagonist also augmented the change in plasma norepinephrine and significantly attenuated the responses of cortisol and renin. Baseline levels of these variables were not altered by the vasopressin antagonist except for an increase in renin activity. Two injections of hypertonic NaCl without any pretreatment produced similar cardiovascular and hormonal responses.
These results suggest that vasopressin contributes not only to an increase in blood pressure, but also to changes in the sympathetic nervous system, the hypothalamo-adrenocortical axis and the peripheral reninangiotensin system in response to a central sodium stimulus.

View full abstract

Two siblings presented with symptoms of left ventricular dysfunction and ventricular arrhythmias. Echocardiography and left ventriculography revealed dilatation, diffuse hypokinesis and apical aneurysm of the left ventricle in both cases. Myocardial infarction was unlikely by history and examinations. We diagnosed them as cases of familial dilated cardiomyopathy complicated by left ventricular aneurysm.

View full abstract

The present report describes a patient with cardiac sarcoidosis who developed complete right bundle branch block, complete atrioventricular block and subsequent congestive heart failure. The patient demonstrated no clinical evidence of systemic sarcoidosis. Upon postmortem examination, the myocardium showed extensive noncaseating granuloma with numerous multinucleated giant cells. An initial routine microscopic examination of the lung revealed no evidence of granulomatous lesions. However, an extensive microscopic examination of the lung using serial sections demonstrated inconspicuous granulomatous lesions with giant cells. Thereby, a diagnosis of sarcoidosis was made. All other organs were free of granulomatous inflammation in spite of an extensive microscopic examination through serial sections. The present case suggests that a careful and extensive microscopic examination of the other organs may be necessary to establish a diagnosis of cardiac sarcoidosis.

View full abstract

A rare case of early stage eosinophilic heart disease was diagnosed by endomyocardial biopsy findings, despite the relatively low peripheral eosinophil blood count (640/mm³).

View full abstract

An echocardiographic study in a patient with cardiac beri-beri has not been reported previously. We report serial studies in a 12-year-old boy with beri-beri. Tricuspid regurgitation was detected by Doppler in the early stage.

View full abstract